Sorafenib zentiva

Package leaflet: Information for the patient

Sorafenib Zentiva, 200 mg, coated tablets
Sorafenibum
Please read all of this leaflet carefully before taking this medicine because it contains
information important for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

1. What Sorafenib Zentiva is and what it is used for
2. Important information before taking Sorafenib Zentiva
3. How to take Sorafenib Zentiva
4. Possible side effects
5. How to store Sorafenib Zentiva
6. Contents of the pack and other information

1. What Sorafenib Zentiva is and what it is used for

Sorafenib Zentiva is used to treat:

• liver cancer (hepatocellular carcinoma).
• advanced kidney cancer (advanced renal cell carcinoma) in patients in whom standard therapy has failed to halt disease progression or is considered inappropriate.
• thyroid cancer (differentiated thyroid carcinoma).

Sorafenib Zentiva is a so-called multi-kinase inhibitor. It works by slowing down the growth of cancer cells and by cutting off the blood supply that supports the growth of cancer cells.

2. Important information before using Sorafenib Zentiva

When not to use Sorafenib Zentiva:

• If the patient is allergic to sorafenib or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Before starting Sorafenib Zentiva, discuss this with your doctor or pharmacist.
When to exercise special caution when using Sorafenib Zentiva

• If skin changes occur. Sorafenib Zentiva may cause rashes and skin reactions, especially on the hands and feet. Usually, these changes can be managed by the treating physician. If they do not resolve, your doctor may temporarily interrupt treatment or discontinue it completely.
• If the patient has high blood pressure. Sorafenib Zentiva may increase blood pressure. Your treating doctor will monitor your blood pressure values and, if elevated, may prescribe medications to lower it.
• If the patient has or has previously had an aneurysm (a weakened and widened blood vessel) or a tear in the wall of a blood vessel.
• If the patient has diabetes. In patients with diabetes, blood glucose levels should be monitored regularly to assess whether the dose of antidiabetic medication needs to be adjusted to minimize the risk of low blood sugar.
• If any bleeding occurs or if the patient is taking warfarin or phenprocoumon. Treatment with Sorafenib Zentiva may increase the risk of bleeding. A person taking warfarin or phenprocoumon, which reduce blood clotting to prevent thrombosis, may have an increased risk of bleeding.
• If chest pain or heart problems occur. Your doctor may decide it is necessary to interrupt or completely discontinue treatment.
• If cardiac disorders occur, such as abnormal electrical activity, known as "QT interval prolongation".
• If surgery is planned or has recently been performed. Sorafenib Zentiva may affect wound healing. Usually, Sorafenib Zentiva is discontinued before surgery. Your treating doctor will decide when to resume treatment with Sorafenib Zentiva.
• If the patient is also taking irinotecan or receiving docetaxel, which are also anticancer medications. Sorafenib Zentiva may enhance their effects, particularly adverse reactions.
• If the patient is taking neomycin or other antibiotics. The effectiveness of Sorafenib Zentiva may be reduced.
• If there is severe liver dysfunction. More severe adverse effects may occur during treatment.
• In case of impaired kidney function. Your doctor will monitor fluid and electrolyte balance.
• Fertility. Sorafenib Zentiva may reduce fertility in both men and women. Any concerns regarding fertility should be discussed with your doctor.
• Gastrointestinal perforation. During treatment, a break in the continuity of the gastrointestinal tract wall may occur (see also section 4: Possible side effects). In such a case, your doctor will recommend discontinuation of treatment.
• If the patient has thyroid cancer. Your doctor will monitor blood levels of calcium and thyroid hormones.
• If the patient experiences any of the following symptoms, contact a doctor immediately, as these may indicate a life-threatening condition: nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, cloudy urine, and fatigue. These symptoms may be caused by a group of metabolic complications that can occur during cancer treatment due to products from the breakdown of dying tumor cells (tumor lysis syndrome, TLS), which may lead to kidney dysfunction and acute kidney failure (see also section 4: Possible side effects).

Inform your doctor if any of the above situations apply to the patient.
In these cases, appropriate treatment may be required, and your doctor may decide to adjust the dosage of Sorafenib Zentiva or discontinue treatment completely (see also section 4: Possible side effects).
Children and adolescents
Studies on the use of Sorafenib Zentiva in children and adolescents have not been conducted.
Sorafenib Zentiva and other medicines
Some medicines may affect the action of Sorafenib Zentiva, or their action may be altered by Sorafenib Zentiva. Inform your doctor or pharmacist about any of the medicines listed below and any other medicines currently or recently taken, or those the patient plans to take, including over-the-counter medicines:

• Rifampicin, neomycin, or other medicines used to treat infections (antibiotics).
• St. John's wort, used in the treatment of depression.
• Phenytoin, carbamazepine, or phenobarbital, medicines used in the treatment of epilepsy and other conditions.
• Dexamethasone, a corticosteroid used in various diseases.
• Warfarin or phenprocoumon, anticoagulant medicines used to prevent blood clots.
• Doxorubicin, capecitabine, docetaxel, paclitaxel, and irinotecan – anticancer medicines.
• Digoxin, used in the treatment of mild to moderate heart failure.

Pregnancy and breastfeeding
Pregnancy should be avoided during treatment with Sorafenib Zentiva. If there is any possibility that the patient could become pregnant, an effective method of contraception should be used during treatment. If a patient becomes pregnant while being treated with Sorafenib Zentiva, she should contact her doctor immediately, who will decide whether treatment can be continued.
Breastfeeding must not be undertaken during treatment with Sorafenib Zentiva, as sorafenib may affect the child's growth and development.
Driving and operating machinery
There are no data indicating that Sorafenib Zentiva may impair the ability to drive or operate machinery.
Sorafenib Zentiva contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, meaning the medicine is considered "sodium-free".

3. How to use Sorafenib Zentiva

This medicine should always be taken exactly as prescribed by the doctor or pharmacist. If in doubt,
contact the doctor or pharmacist.
The recommended dose of Sorafenib Zentiva in adults is 2 tablets of 200 mg twice daily.
This corresponds to a daily dose of 800 mg or four tablets per day.
Sorafenib Zentiva tablets should be swallowed with a glass of water, on an empty stomach or with a
meal low or moderate in fat. Do not take the medicine with high-fat meals, as this may reduce the
effectiveness of Sorafenib Zentiva. If a high-fat meal is planned, the tablets should be taken at least
1 hour before or 2 hours after the meal. This medicine should always be taken as directed by the doctor. In case of
doubt, consult the doctor or pharmacist.
It is important to take this medicine at approximately the same time each day to ensure a constant
level of medicine in the bloodstream.
This medicine is usually taken for as long as it provides clinical benefit and as long as the patient does not
experience unacceptable side effects.
Taking more Sorafenib Zentiva than recommended
Immediately inform the doctor if the patient (or anyone else) has taken more than the recommended dose.
Taking too much Sorafenib Zentiva may increase the risk or severity of adverse reactions, especially diarrhoea and skin reactions. The doctor may advise stopping treatment with this medicine.
Missing a dose of Sorafenib Zentiva
If a patient misses a dose, they should take it as soon as they remember.
If the next scheduled dose is approaching, the missed dose should be skipped and the patient should continue treatment as before. Do not take a double dose to make up for a missed dose.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone experiences them.
This medicine may affect the results of certain blood tests.

Very common:
may occur in more than 1 in 10 people

• Diarrhoea;
• Nausea;
• Feeling of weakness or fatigue;
• Pain (including oral pain, abdominal pain, headache, bone pain, tumour-related pain);
• Hair loss (alopecia);
• Redness or pain in the palms of the hands or soles of the feet (hand-foot syndrome);
• Itching or rash;
• Vomiting;
• Bleeding (including cerebral haemorrhage, intestinal wall bleeding, respiratory tract bleeding; haemorrhage);
• High blood pressure or periodic increases in blood pressure (hypertension);
• Infections;
• Loss of appetite (anorexia);
• Constipation;
• Joint pain (arthralgia);
• Fever;
• Weight loss;
• Dry skin.

Common:
may occur in not more than 1 in 10 people

• Flu-like symptoms;
• Indigestion (dyspepsia);
• Difficulty swallowing (dysphagia);
• Inflammation or dryness in the mouth, tongue pain (stomatitis, mucosal inflammation);
• Low blood calcium levels (hypocalcaemia);
• Low blood potassium levels (hypokalaemia);
• Low blood sugar levels (hypoglycaemia);
• Muscle pain (myalgia);
• Sensory disturbances in fingers and toes, including tingling or numbness (peripheral sensory neuropathy);
• Depression;
• Erectile dysfunction (impotence);
• Voice changes (dysphonia);
• Acne;
• Skin inflammation, dry and flaking skin (dermatitis, skin desquamation);
• Heart failure;
• Heart attack (myocardial infarction) or chest pain;
• Tinnitus (ringing in the ear);
• Kidney failure;
• Exceptionally high protein levels in urine (proteinuria);
• General weakness or loss of strength (asthenia);
• Decreased white blood cell count (leukopenia and neutropenia);
• Decreased red blood cell count (anaemia);
• Low platelet count (thrombocytopenia);
• Inflammation of hair follicles (folliculitis);
• Reduced thyroid activity (hypothyroidism);
• Low blood sodium levels (hyponatraemia);
• Taste disturbances (dysgeusia);
• Redness of the face and often other skin areas (flush);
• Watery nasal discharge (watery rhinitis);
• Heartburn (gastroesophageal reflux disease);
• Skin cancer (squamous cell carcinoma/skin squamous cell carcinoma);
• Thickening of the outer skin layer (hyperkeratosis);
• Sudden, involuntary muscle cramps (muscle cramps).

Uncommon:
may occur in not more than 1 in 100 people

• Inflammation of the mucous lining of the stomach;
• Abdominal pain due to inflammation of the pancreas, inflammation of the gallbladder and/or bile ducts;
• Yellowing of the skin or eyes (jaundice) caused by high levels of bile pigments (hyperbilirubinaemia);
• Allergic reactions (including skin reactions and urticaria);
• Dehydration;
• Breast enlargement (gynaecomastia);
• Breathing difficulties (lung disease);
• Rash (eczema);
• Increased thyroid activity (hyperthyroidism);
• Various skin eruptions (erythema multiforme);
• Exceptionally high blood pressure;
• Perforation of the intestinal wall (gastrointestinal perforation);
• Reversible swelling of the posterior part of the brain, which may be associated with headache, altered consciousness, seizures, and visual disturbances including loss of vision (reversible posterior leukoencephalopathy);
• Sudden, severe allergic reaction (anaphylactic reaction).

Rare:
may occur in not more than 1 in 1,000 people

• Allergic reaction with skin swelling (e.g. face, tongue), which may cause breathing or swallowing difficulties (angioedema);
• Irregular heart rhythm (QT interval prolongation);
• Inflammation of the liver, which may cause nausea, vomiting, abdominal pain and jaundice (drug-induced hepatitis);
• Sunburn-like rash, which may occur on skin previously exposed to radiation therapy, and may be severe (radiation-induced dermatitis);
• Severe skin and/or mucosal reactions, including painful blisters and fever, including extensive skin peeling (Stevens-Johnson syndrome and toxic epidermal necrolysis);
• Abnormal breakdown of muscle tissue, which may lead to kidney dysfunction (rhabdomyolysis);
• Kidney damage causing loss of large amounts of protein (nephrotic syndrome);
• Inflammation of blood vessels in the skin, which may cause a rash (leukocytoclastic vasculitis).

Unknown:
frequency cannot be determined from available data

• Brain function disorders, which may be associated with, for example, drowsiness, behavioural changes or disorientation (encephalopathy);
• Enlargement and weakening of a blood vessel wall or tearing of the blood vessel wall (aneurysm and arterial dissection).
• Nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, cloudy urine and fatigue [tumour lysis syndrome (TLS)] (see section 2).

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181 C
02 222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder or its representative in Poland.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Sorafenib Zentiva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the outer carton and
blister pack after “EXP”. The expiry date refers to the last day of the stated month.
Do not store above 30°C.
Medicines should not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines no longer required. Such measures will help
protect the environment.

6. Contents of the pack and other information

What Sorafenib Zentiva contains

• The active substance is sorafenib. Each coated tablet contains 200 mg of sorafenib (as tosylate).
• The other ingredients are:
  Tablet core: hypromellose 2910, sodium croscarmellose, microcrystalline cellulose, magnesium stearate, sodium lauryl sulphate.
  Tablet coating: hypromellose 2910, titanium dioxide, macrogol, iron oxide red (E 172).

What Sorafenib Zentiva looks like and contents of the pack
Sorafenib Zentiva 200 mg coated tablets are red-brown, round, biconvex, film-coated tablets with "200" embossed on one side and smooth on the other, with a diameter of 12.0 mm ± 5%.
The tablets are packed in aluminium/PVC/PE/PVDC blisters containing 112 film-coated tablets, in a cardboard carton.
The tablets are also packed in perforated single-dose aluminium-PVC/PE/PVDC blisters containing 112 x 1 film-coated tablet, in a cardboard carton.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Zentiva, k.s.,
U kabelovny 130
Dolní Měcholupy
102 37 Prague 10
Czech Republic

Manufacturer
Remedica Ltd
Aharnon Street, Limassol Industrial Estate
3056 Limassol
Cyprus
PharOS MT Ltd.
HF62X, Hal Far Industrial Estate, Birzebbugia BBG3000
Malta

This medicinal product is authorised in the European Economic Area countries under the following names:
Estonia, Italy, Poland, Slovakia,
Czech Republic: Sorafenib Zentiva
Netherlands: Sorafenib Zentiva 200 mg, filmomhulde tabletten
France: SORAFENIB ZENTIVA 200 mg, comprimé pelliculé
Latvia: Sorafenib Zentiva 200 mg apvalkotās tablets
Lithuania: Sorafenib Zentiva 200 mg plėvele dengtos tabletės
Bulgaria: Сорафениб Зентива 200 mg филмирани таблетки
Romania: Sorafenib Zentiva 200 mg comprimate filmate
United Kingdom (Northern Ireland): Sorafenib Zentiva 200 mg film-coated tablets